ReviewJournal of molecular medicine (Berlin, Germany)2008
A central role for free heme in the pathogenesis of severe malaria: the missing link?
Review in Journal of molecular medicine (Berlin, Germany), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- Research hotspots and future trends in sepsis-associated acute kidney injury: a bibliometric and visualization analysis.Frontiers in medicine · 2024Pooled it
- Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis.Scientific reports · 2018Trial
- Hypomorphic biliverdin reductase a mutations define bilirubin anti-malarial threshold.iScience · 2026Article
- Article
- The mechanisms by which free heme exacerbates sepsis and the potential therapeutic targets.Frontiers in immunology · 2026Review
- Plasma haem oxygenase-1 and interleukin-6 as adjunct host biomarkers associated with malaria.Frontiers in immunology · 2026Article
- Heme oxygenase-1 and malaria pathogenesis.Frontiers in immunology · 2026Review
- Article
- Application of Multiplatform Mass Spectrometry to the Study ofInternational journal of molecular sciences · 2025Article
- A metabolite-based resistance mechanism against malaria.Science (New York, N.Y.) · 2025Article
- Phenotype and function of IL-10-producing NK cells in individuals with malaria experience.JCI insight · 2025Article
- Ferritin heavy chain supports stability and function of the regulatory T cell lineage.The EMBO journal · 2024Article
- Targeting circulating labile heme as a defense strategy against malaria.Life science alliance · 2024Article
- Major endothelial damage markers identified from hemadsorption filters derived from treated patients with septic shock - endoplasmic reticulum stress and bikunin may play a role.Frontiers in immunology · 2024Article
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Fluorescent silicon nanoparticle-based quantitative hemin assay.Analytical and bioanalytical chemistry · 2022Article
- Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice.Nature communications · 2022Article
- Maresin conjugates in tissue regeneration-1 suppresses ferroptosis in septic acute kidney injury.Cell & bioscience · 2021Article
- Combined Transcriptome and Proteome Profiling for Role of pfEMP1 in Antimalarial Mechanism of Action of Dihydroartemisinin.Microbiology spectrum · 2021Article
- Trained innate immunity, long-lasting epigenetic modulation, and skewed myelopoiesis by heme.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malaria, the disease caused by Plasmodium infection, is endemic to poverty in so-called underdeveloped countries. Plasmodium falciparum, the main infectious Plasmodium species in sub-Saharan countries, can trigger the development of severe malaria, including cerebral malaria, a neurological syndrome that claims the lives of more than one million children (<5 years old) per year. Attempts to eradicate Plasmodium infection, and in particular its lethal outcomes, have so far been unsuccessful. Using well-established rodent models of malaria infection, we found that survival of a Plasmodium-infected host is strictly dependent on the host's ability to up-regulate the expression of heme oxygenase-1 (HO-1 encoded by the gene Hmox1). HO-1 is a stress-responsive enzyme that catabolizes free heme into biliverdin, via a reaction that releases Fe and generates the gas carbon monoxide (CO). Generation of CO through heme catabolism by HO-1 prevents the onset of cerebral malaria. The protective effect of CO is mediated via its binding to cell-free hemoglobin (Hb) released from infected red blood cells during the blood stage of Plasmodium infection. Binding of CO to cell-free Hb prevents heme release and thus generation of free heme, which we found to play a central role in the pathogenesis of cerebral malaria. We will address hereby how defense mechanisms that prevent the deleterious effects of free heme, including the expression of HO-1, impact on the pathologic outcome of Plasmodium infection and how these may be used therapeutically to suppress its lethal outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.